Zifu Li
National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, China
Title: Combined administration by nanomedicine: an effective treatment against insufficient chemotherapy-promoted tumor metastasis
Biography
Biography: Zifu Li
Abstract
Statement of the Problem: Although nanoparticles could enhance the delivery efficiency of chemotherapeutics, the percentages accumulating at tumor site is still low, with a median of 0.7% for the last decade. Tumor tissue with insufficient chemotherapy might be the crime culprit of tumor metastasis. In this research, we adopted a combined-administration strategy by nanoparticle to prevent the insufficient chemotherapy-promoted tumor metastasis. DOX and TGF-β receptor inhibitor, LY2157299, were co-delivered by HES-PLA nanoparticle. With suppression of EMT process by blocking the TGF-β path, the distant metastasis were dramatically inhibited. Meanwhile, DOX exhibited better anti-tumor efficacy on the primary tumor.
Methodology & Theoretical Orientation: HES-PLA nanoparticles was obtained by a three-step preparation procedure and characterized by TEM, AFM and DLS. Anti-tumor efficacy in vitro was evaluated with 4T1 cell by MTT assay. Western blot was applied to evaluate the expression of EMT-related proteins. ELISA was used to quantify TGF-β. The metastatic capabilities of cell treated with different administrations were evaluated by transwell assay (in vitro) and zebrafish model (in vivo). Mice bearing subcutaneous 4T1 tumor were ultimately used to examine its efficacy of anti-primary tumor and anti-distant metastasis.
Findings: The transwell assay and zebrafish model reveal that low dose of DOX could enhance the metastasis ability of 4T1 cell. Importantly, the in vivo study demonstrate that co-deliver of DOX and LY2157299 by nanoparticle could simultaneously suppress the primary tumor (TIR, 80.7%) and distant metastasis (no nodule on the lung).
Conclusion & Significance: In vivo biological barriers always deteriorate the delivery efficacy of DOX, causing insufficient chemotherapy and therefore promoting metastasis. Combined administration of DOX and LY2157299 could significantly suppress the insufficient-chemotherapy-enhanced EMT process by blocking the TGF-β path, decreasing the distant metastasis and intensifying the anti-tumor efficacy of DOX.